Modern - Blog Science Connections

induction in vivo by the RNA retroviruses. It is
still a major puzzle that similar or identical
genomes can induce quite different malignaneies,
as observed for example in the induction
of tumors as different as fibrosarcomas, melanomas,
and glioblastomas by a single strain of
Rous sarcoma virus, and that the same malignancy
can be initiated by different viral genomes.
I am sure that the pathogenicity of these
diseases will be understood much better during
the coming years, although this understanding
will be achieved not only by analysis of the
genomes down to the last base pair but more by
examination of the total process of transformation,
i.e., the virus, the route of infection, the
type and physiologic state of the infected cells,
and the response of the total organism to the
emergence of transformed cell clones.
There was relatively little discussion of
DNA tumor viruses, except for an overview of
the structure of the primate lymphotropic
herpesviruses and discussions of the pathogenesis
of Epstein - Barr virus (EBV) infections.
The pathogenic events leading from primary
lymphoproliferative EBV infections to complete
recovery with a lifelong carrier state and
the development later of monoclonal malignancies
or an immediate progression of an
acute monucleosis into a malignant fatallymphoproliferative
disease are particularly interesting
and deserve intensive study. The report
of lytic activity of EBV is important for two
reasons: it allows better study in vitro of EBV
and it may explain the infection of epithelial
cells in vivo. Of importance also is the demonstration
of EBV genomes in normal parotic
cells whieh may answer the old question of
where EBV multiplies during the long periods
of oral excretion.
On reflecting generally on the viral studies
I want to repeat a caution sounded often
before : We must not ignore the fact that some
of our virus models, and I am referring
particularly to the avian and murine retroviruses,
are highly artificial, using inbred selected
animals and laboratory-propagated and perhaps
laboratory-created viruses, whose rele­
\Wlnce to naturally occurring disease is at least
in part questionable, although their value for
a basic understanding of cell function and
regulation is undisputed. Studies in outbred
animal populations, such as cats and cattle,
may be more comparable to reallife. Particularly
intriguing is the situation of "virus-free"
cat leukemias in which the virus might have
acted as a "hit and run" villain, leaving either
only a small part of itself behind or changing
only the genes responsible for cell regulatory
mechanisms without a need for persistence of
any part of the viral genome, a mechanism
which has also been considered for the transformation
of cells by some DNA viruses,
particularly the herpesviruses.
In yesterday's sessions we heard about very
exciting developments in cell biology and
immunology. The differentiation of the cells of
the hematopoietic and the immune systems
into many highly specialized cell subpopulations
has been analyzed in detail, thus allowing
a much finer and detailed analysis of the
immune mechanisms whieh play a role in the
emergence of tumors and the defense of the
organism against them. Use of monoclonal
antibodies has alm ost revolutionized this field,
and it will be most interesting to study not only
the physiologie and immunologie functions
and antigenie identities of the various cell types
but also their susceptibility to exogenous viral
infection, to activation of endogenous viral
genes, and to chemical or physical carcinogens.
The development of cell culture techniques
and separation of various cell populations have
progressed rapidly and already have improved
our understanding of normal differentiation
and of regulatory disturbances leading to
malignant transformation, although this is
another area in whieh we must remember that
isolated cells in vitro may behave quite differently
from cells in the intact organism with its
multiple cell interactions and regulatory mechanisms,
to which we should add Dr. Moore's
new ly defined "oncgene" -mediated "pericrine"
controls as well as still unidentified influences.
The report of thymic nurse cells within which
differentiation of other cells seems to occur is
an intriguing observation, the general significance
of which needs further exploration. In
addition the nude thymusless, the spleenless,
and the very special mice lacking both of these
organs are now joined by the "beige mouse,"
astrain whieh is deficient for natural killer cells
and wh ich will permit a further disseetion of
the immune defenses against tumor development.
The new perspective of the various,
specific chromosomal aberrations in different
diseases should stimulate furt her research to
relate specific chromosomal to specific pathologie
changes, and in this respect the studies on
the X-linked lymphoproliferative syndrome
(Duncan's disease) which is associated with
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